On future missions into deep space, astronauts will be required to work more autonomously than on previous missions, and thus their ability to perform executive functions could be critical to mission success. In this study, we determined the effect that ≤15 cGy of 600 MeV/n ⁵⁶Fe particles has on attentional set-shifting (ATSET) performance of ∼10 month-old (at the time of irradiation) male Wistar rats that had been prescreened for their ability to perform the task. Exposure to 1-15 cGy of ⁵⁶Fe particles leads to a significant impairment in compound discrimination (CD) performance. Should similar effects occur in astronauts, an impaired ability to execute CD would result in a decreased ability to identify and maintain focus on relevant aspects of the task being performed. The use of rats that had been prescreened for ATSET performance helped to establish that working memory of the rules for the food reward remained intact (for at least 100 days) even after 15 cGy irradiation with 600 MeV/n ⁵⁶Fe particles, but that ⁵⁶Fe radiation exposure affected associative cue learning/acquisition rather than an intrinsic inability to perform the CD tasks. Our data suggest that declarative memory, and the ability to transitively infer established rules, also remained intact in the irradiated rats. Thus, should similar effects occur in astronauts, ⁵⁶Fe-induced CD performance deficits may only be manifested in scenarios where astronauts are required to transitively apply their knowledge to solve problems that they have not previously encountered; nevertheless, potentially one-third of astronauts may not be able to perform event-critical tasks correctly. The implication of this data, from a probabilistic risk assessment perspective, is that cognitive performance studies that use naïve rodents, thus requiring task rule acquisition as well as task performance, are likely to overestimate the risk of ⁵⁶Fe-induced cognitive deficits.

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